| Natural products containing the 1,3-polyol moiety are an important class of compounds with a wide range of biological activities. These natural products have demonstrated significant biological activities including plant growth inhibition, as well as antifeedent, antifungal, anti-inflammatory, antibacterial, and antitumor properties. Although several strategies have been developed to synthesize the 1,3-polyol structural motif, there still exists a need for a more efficient asymmetric catalysis approach to these complex molecules. In particular, we investigated a catalytic osmium-palladium, oxidation-reduction approach to these important targets.; Crucial to this methodology was the development of an efficient, stereoselective route to synthesize δ-hydroxy enoates. Our approach started with the use of a Sharpless asymmetric dihydroxylation of a dienoate. A cyclic carbonate was then prepared by treating a solution of the diol with triphosgene. Treatment of the cyclic carbonate with a catalytic amount of palladium and triphenylphosphine, and a mild hydride source, afforded the desired δ-hydroxy enoate. The alcohol was then reacted with benzaldehyde in the presence of catalytic base to produce a benzylidene-protected syn-3,5-dihydroxy carboxylic ester in good yield and excellent selectivity. An allyl addition/metathesis/base-catalyzed benzylidene formation reaction sequence on benzylidene-protected syn-3,5-dihydroxy carboxylic esters allowed access to the syn, syn, syn-1,3-polyol motif. An iterative palladium/osmium, oxidation/reduction reaction sequence allowed access to syn, syn, syn- and syn, anti, syn-1,3-polyols.; The osmium-palladium (oxidation-reduction) reaction sequence was applied toward the synthesis of the even-numbered 1,3-polyol/pyranone natural product tarchonanthuslactone and the odd-numbered 1,3-polylol/pyranone natural product cryptocarya diacetate. The efficiency of our osmium/palladium approach toward δ-hydroxy enoates was also demonstrated in the total syntheses of the unsymmetrical bis-lactone natural products colletodiol, colletol, and grahamimycin A. Using methodology that was developed for the synthesis of benzylidene-protected pseudo-symmetric diols, significant progress was made toward the synthesis of leucascandrolide A. |
